The objective of the work proposed here is to carry out an investigation of the structure of a regulatory protein involved in the control of gene expression. The methods involve a combination of genetics and physical chemistry. m-Fluorotyrosine will be incorporated into wild type and a variety of suppressed nonsense mutations in the lactose operon repressor of E. coli. The structure of this protein will then be studied by observing changes in the fluorine-19 NMR spectrum upon interaction with inducers, anti-inducers and DNA. Since the procedure used for incorporating the tyrosine analogue involves the use of lambda phage, this approach will also be applied to the lambda cro gene product. Using the same methods that have been developed, we will extend these studies to fluorine analogues of leucine, isoleucine and valine. This lactose operon repressor and the lambda cro gene product interact with specific DNA sequences and thus serve as prototype systems for the study of the protein nucleic acid interactions involved in gene regulation and chromosome structure.